Immunosuppressive drugs for renal disease
Some types of kidney damage occur through activation of the immune system causing inflammation. Lupus (SLE) affecting the kidney, vasculitis, and Goodpasture’s disease are all diseases in which kidney damage is caused by inflammation. So are several types of glomerulonephritis. Immunosuppressive drugs and drugs that reduce inflammation are used to treat these diseases. Immunosuppressive drugs are essential in kidney transplants to dampen the immune system and prevent rejection. Some other kidney diseases are slower but also respond to treatment of this type, for example some causes of nephrotic syndrome.
- Cyclosporin and tacrolimus
- MMF (mycophenolate mofetil)
- Plasma exchange
- Rituximab and other antibodies
- Other treatments
Steroids, for example prednisolone, prednisone and methyl prednisolone, are useful and are the most commonly prescribed immunosuppressive drugs. Their full description is corticosteroid
- Weight gain through increased appetite and fluid retention
- Raised blood pressure
- Diabetes, in some patients
- Thinning of bones – osteoporosis
- Thinning of skin and easy bruising
- Risk of serious infections
Doses are reduced as soon as possible, and in some conditions they may not now be essential, but for many conditions no alternative agent has yet been developed that can completely replace the use of steroids.
If steroids are taken for a long time, the body stops producing its own steroid hormone. Suddenly stopping steroid treatment after it has been taken for a long time can then be dangerous, as the sudden shortage of steroid hormones causes an Addisonian crisis. Therefore steroid treatment is often reduced slowly to allow the adrenal glands to recover. However in the six months after you have stopped steroid treatment, an infection or other illness may increase the body’s need for steroids, and you may need to start treatment with steroids again. It is recommended that anyone who is taking steroids should carry a STEROID CARD so that medical staff will know about your steroid treatment if you have any other health problems. You should continue to carry it for at least six months after stopping treatment, too.
Here are some ways to counteract the bone thinning (osteoporosis) effects of steroid therapy:
- Calcium and Vitamin D supplements.
- Bisphosphonates (many types, e.g. pamidronate, etidronate) are drugs that can reduce bone loss during treatment, and may be used to increase bone strength in osteoporosis.
For patients receiving steroids for a long time, their long-term safety is not completely proved.
- Hormone replacement therapy (HRT) may help in women, after the menopause.
- Other treatments are being developed.
Patients who have had reduced kidney function for some time (e.g. years at eGFRs below 30) bone scans to look for osteoporosis may be misleading, as you may also have renal bone disease. Reduced kidney function can also limit the treatment options for osteoporosis.
This is a powerful drug that attacks white blood cells. It is especially effective in several types of vasculitis that were often fatal in the past, and in SLE and in other conditions. However the drug has some serious side-effects:
- Serious infections and bleeding – blood count must be checked regularly.
- Bladder irritation may cause cystitis and bleeding.
- It may lead to infertility in men through toxic effects of the drug on sperm, (usually following prolonged treatment, over more than 3 months of daily treatment). Sperm can be collected before the treatment starts if time permits.
- In women it may cause infertility and premature menopause through toxic effects on the ovaries (usually after prolonged treatment).
- It is toxic to unborn babies.
- There is a slightly increased risk of bladder cancer in later life.
- There is a slightly increased risk of leukemia in later life.
Keeping the courses short (three months) reduces the risk of toxic effects from cyclophosphamide. Administering it in the form of an injection every two to four weeks, rather than as a daily dose by mouth, can also keep the total dose down. This seems to be just as effective in most circumstances.
This drug has similar side-effects to cyclophosphamide but is less powerful and generally safer. It does not affect fertility or the bladder, and can be used safely in pregnancy. Azathioprine must be monitored with blood counts and has an increased risk of infection. It is often used after a course of cyclophosphamide in severe vasculitis, or at the outset in milder vasculitis or milder SLE. Azathioprine is also used to prevent rejection in kidney transplants and can be used in some kinds of glomerulonephritis. There is an important side effect for people who are taking azathioprine for a long time:
- People on azathioprine for a long time are at risk of developing some skin tumours. It is important to avoid sunbathing and to use sun blocking creams.
Mycophenolate mofetil (MMF)
MMF is a newer drug which works in a similar way to azathioprine. It is more powerful, but carries extra risks of infection. It is used in transplantation to prevent rejection, and also in vasculitis and SLE. It is also being used in some other kidney diseases. MMF is usually used with steroids. Most of its serious side effects are similar to other drugs of this type. Side effects include:
- Stomach upset, including diarrhoea and vomiting. Improves with dose reduction.
- Risk of serious infections.
- Risk of bleeding and easy bruising.
- Risk of some cancers with long term treatment.
- Risk to baby in pregnancy
MMF and closely related drugs are proved to be very damaging to developing babies. They may cause malformations or miscarriage. If you are a woman you should use very reliable contraception while taking it, and for at least 6 weeks after stopping it.
It is also recommended that men should not father children while taking MMF, or for 3 months after stopping it, although this recommendation is being questioned.
If this is an issue for you, discuss this with your medical team. It may be possible to switch you to a safe alternative such as azathioprine. Don’t stop MMF without advice. Remember that it is not safe for babies to have a sick mother either.
Methotrexate is used to treat some cancers. It can be used to treat inflammation in some types of arthritis and sometimes in vasculitis. In vasculitis and arthritis it is usually given once a week, with folic acid (a vitamin) being given 1-3 days later. Regular tests for blood count and liver function are required. Methotrexate should not be used in pregnancy. It is normally removed by the kidney, so it cannot usually be used in people with significantly reduced kidney function. Side effects can include:
- Hair loss
- Mouth ulcers and diarrhoea
- Liver damage (rare)
- Lung damage causing shortness of breath and cough (rare)
- Risk of infections and bleeding
- Toxic to developing babies
Cotrimoxazole is an antibiotic combination (also known as Septrin, Bactrim) which can sometimes be used in some types of vasculitis, particularly Wegener’s disease (Granulomatosis with angiltis). It is probably less useful in kidney and lung vasculitis. The main side effects are gastric upset and occasional allergic reactions.
The same antibiotic is often used to prevent ‘Pneumocystis’ pneumonia in patients who are heavily immunosuppressed (e.g. receiving high doses or several of the drugs on this page). Pneumocystis pneumonia can be a problem in people with a weakened immune system.
Cyclosporin (ciclosporin) and tacrolimus
Cyclosporin (now officially spelled ciclosporin) and tacrolimus are powerful drugs to dampen the immune response. They are mainly used in transplantation, but occasionally are used in kidney diseases, especially in nephrotic syndrome. Side-effects may be troublesome. Cyclosporin can sometimes cause tremor, and excessive hair growth, especially on the face, and gum swelling. There are some other rarer side effects. Tacrolimus may also cause tremor, and can cause upset sleep or headaches. Occasionally it causes feeling sick, and pins and needles in the arms and legs.
Both ciclosporin and tacrolimus can cause kidney damage themselves, which always has to be balanced with potential benefits.
Both medications work in a similar way. People taking these medicines are more likely to develop infections, including some unusual ones. Being on these tablets over a long time can increase the risk of some tumours and it is recommended to avoid sunbathing and always wear sunblock in sunny weather to protect against skin cancer. You should watch out for the development of lumps and bumps on the skin and report these to your doctor if they occur. Women should have regular cervical smears.
This is a treatment in which a volume of plasma is removed and discarded and replaced by a plasma substitute taken from blood donors. It involves pumping blood through a machine for between one and two hours, and is usually given every day and then perhaps on alternate days for a short period.
The aim is usually to remove antibodies, but sometimes it is used to supplement or replace important plasma proteins. Plasma exchange is most useful during severe disease before other treatments have had time to work, and is not usually effective on its own. Usually the patient’s plasma is replaced with a very pure protein called albumin. However it may be necessary to use frozen plasma or other proteins from plasma. These carry similar risks to blood transfusions. There is some risk of causing or worsening bleeding, because clotting factors are removed, and thinning of the blood is required to allow the machine to work.
Immunoadsorption is a treatment in which antibodies are removed without removing plasma. Less replacement is therefore required, and the treatment may be more efficient at removing antibodies. However the treatment is complex and long, and the machines required (and skilled operators) are not widely available. For some diseases it may not be as good as plasma exchange, but if antibody removal is very important it may be more effective.
IVIG stands for intravenous immunoglobulin. Immunoglobulin = antibodies, proteins in the blood that are made in the bone marrow by ‘B’ cells of the immune system, mainly to fight infection.
IVIG is given by intravenous infusion. It is used:
- in patients with low levels of immunoglobulin, to prevent infection.
- in patients with some autoimmune conditions where antibodies attack.
It isn’t fully understood how supplementing antibodies works in autoimmune conditions, but it is effective in some. It is of proven benefit in Kawasaki disease (a type of vasculitis that usually occurs in children), although it helps in a number of autoimmune conditions where antibodies attack parts of the body
Antibodies to lymphocytes and other blood cells
Rituximab and anti-B cell antibodies
B cells (B Lymphocytes) are cells in the bone marrow which develop into plasma cells that produce antibodies. Rituximab is an artificially produced antibody that attacks B lymphocytes, a single dose (or 2 doses) lowering B cell counts for many months. This has only slow effects on antibody levels, as the plasma cells that are producing antibodies are not targeted by the antibody. However Rituximab and other B cell antibodies seems to reduce autoantibody levels slowly in some conditions, and can also help in some other autoimmune diseases, even when autoantibodies aren’t obviously the problem.
Rituximab is a mouse-type antibody. Some others are closer to human antibodies, less likely to cause some allergic-type side effects.
ATG – antithymocyte globulin
T cells (Thymocytes) are important in almost all immune responses and are the major players in many responses – including especially those where there are no antibodies involved. ATG and ALG are anti-T lymphocyte antibodies made in animals (rabbits or horses). They are very effective in anti-rejection treatments in kidney transplantation, and are sometimes used in autoimmune conditions too.
This is another artificial antibody that kills a lot of T lymphocytes and some other cells. It is engineered to be like a human antibody, and like some anti-B cell antibodies, its effects last for months. It is used in transplantation, some cancers, and some autoimmune conditions, including small vessel vasculitis.
Anti-TNF antibodies and other similar treatments are under investigation in a number of aggressive types of kidney inflammation.
Acknowledgements: The authors of this page were Gemma Browne and Neil Turner. It was first published in June 2000, with major revisions in February 2016. The date is was last modified is shown in the footer.